Background The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4–8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35–65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9–18.8), piperacillin was 78.6 mg/L (49.5–127.3), tazobactam was 9.5 mg/L (6.3–14.2), and vancomycin was 14.3 mg/L (11.6–21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

No abstract

No abstract

Background: Community-acquired pneumonia is a frequent cause for hospital admission that results in significant costs to the health care system. The length of hospital stay (LOS) affects costs as well as risk for nosocomial medical complications. The purpose of this study was to test whether the addition of intensive clinical case management to clinical guidelines could lead to a reduction in LOS that was not achievable by guidelines alone, while maintaining quality of care. Methods: Patients were studied in 3 sequential blocks at a single hospital from November 2002 to February 2005. Block 1 patients (n=110) were given conventional treatment. For block 2 (n = 119), guidelines and/or standardized order sets (SOSs) were used supported by intensive clinical case management (ICCM) (full variance tracking with concurrent feedback and reminders). The ICCM interventions were conducted by resident physicians. For block 3 (n = 115), all orders were written with guidelines and/or SOSs but without ICCM. Results: The mean±SD time to clinical stability was not significantly different between the groups (block 1, 3.3±1.4 days; block 2, 3.2±1.2 days; and block 3, 3.4±1.3 days). The mean LOS was significantly lower in block 2 (5.3±3.5 days) than in blocks 1 (8.8±4.4 days) (PϽ.001) and 3 (7.3±3.9 days) (PϽ.01) and significantly lower in block 3 than in block 1 (P=.05). Time to change to oral antibiotics was earlier in block 2 (3.7±0.9 days) than in blocks 1 and 3 (5.7±2.4 and 5.0±1.9 days, respectively) (PϽ.001). The mean time from clinical stability to hospital discharge was significantly shorter for block 2 (2.1±2.2 days) than for blocks 1 (5.3±4.4 days) (PϽ.001) and 3 (4.9±4.2 days) (PϽ.001). Patients in block 2 had a greater proportion with progressive ambulation (PϽ.001), pneumococcal (PϽ.001) or influenza vaccination (PϽ.01), deepvenous thrombosis prophylaxis (P=.01), and smoking cessation counseling (P=.01). There was no significant difference between the blocks in mortality or hospital readmission rate. Conclusions: The combined intervention of SOS plus ICCM led to a substantial reduction in LOS while maintaining quality of care. The main effect occurred by reducing the time from clinical stability to discharge, which appeared to be the key "modifiable" process of care adding to a prolonged LOS.